Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (OCO). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case for 10,000 girls. Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consisstent with an autosomal dominant form of inheritance. Neurobiologic and pharmacological data have implciated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and the basal ganglia and frontal cortex remain the prime candidates as the neuroanatomical origin for TS related pathology. The long term objective of this project is to identify and localize the neurobiological mechanisms repsonsible for TS. During the first four years of this project, we seek the following objectives: 1. Collect and assay CSF from 200 "drug-free" patients and controls in an effort to identify the neurochemical and neuropeptide systems associated with the expression of TS and related disorders, particularly OCD. Based on preliminary data, we are especially interested in the potential role of dynorphin A and its relationship to central dopaminergic and serotonergic systems in TS and OCD patients. 2. Assessment of the clinical severity of TS and OCD symptoms using valid and reliable rating instruments. These data will be analyzed in an effort to define the clinical correlates of the CSF data. 3. Assessment of first degree family members of the patients using direct interview techniques in order to determine the pattern of familial aggregation of TS and OCD symptoms and to establish the relationship, if any, between the CSF findings and the pattern(s) of familial aggregation. Over the past decade, a critical mass of investigators at Yale have focused on TS and related disorders. This project will benefit from the clinical, genetic and neuropathological studies of TS ongoing at Yale.